Inside-Out versus Outside-In models for virus induced demyelination: axonal damage triggering demyelination.
Inside-Out versus Outside-In models for virus induced demyelination: axonal damage triggering demyelination.
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DOI：
10.1007/s00281-002-0105-z
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Fujinami RS
中科院分区：
文献类型：
--
作者：
Tsunoda I;Fujinami RS
多发性硬化症(MS)的主要靶点被认为要么是髓鞘本身(髓鞘病)，要么是髓鞘形成细胞-少突胶质细胞(少突胶质病)。虽然轴突损伤发生在MS中，但它被认为是髓鞘损伤的继发性事件。在这里，病变从髓鞘(外部)发展到轴突(内部)(自外向内模型)。最近，在MS中也报告了灰质损伤和轴突损伤，看起来正常的白质。这提出了两个问题。1)轴突损伤是仅继发于髓鞘损伤，还是直接损害轴突或神经元(轴索病变)？(2)轴突损伤是否仅被视为病理或疾病的最终结果，或者轴突损伤是否有助于继发性损伤的扩散，包括脱髓鞘？前者是因为已有报道在几种病毒感染中发现轴突损伤，包括人类免疫缺陷病毒、人类T淋巴细胞趋化病毒1、单纯疱疹病毒和冠状病毒，这些病毒也会导致脱髓鞘。轴突损伤导致其他改变的后一种可能性是由于脊髓损伤(SCI)和MS之间出人意料的相似，轴突损伤、少突胶质细胞凋亡和脱髓鞘都存在。在脊髓损伤中，轴突横断导致迟发性少突胶质细胞凋亡并继发脱髓鞘。脊髓切片神经丝免疫染色显示，在多发性硬化的动物模型中，伴有少突胶质细胞凋亡的轴突损伤也先于脱髓鞘，泰勒氏鼠脑脊髓炎病毒感染。这意味着轴突损伤可能引发脱髓鞘。在这种情况下，病变从轴突(内)发展到髓鞘(外)(内向外模式)。
The primary target in multiple sclerosis (MS) is believed to be either myelin itself (myelinopathy) or the myelin-forming cell, the oligodendrocyte (oligodendrogliopathy). Although axonal injury occurs in MS, it is regarded as a secondary event to the myelin damage. Here, the lesion develops from myelin (outside) to the axon (inside) (Outside-In model). Recently, gray matter lesions and axonal injury in normal-appearing white matter have also been reported in MS. This raises two questions. 1) Is axonal injury exclusively secondary to myelin damage or from a direct insult to the axon or neurons (axonopathy)? (2) Is the injured axon regarded as only an end result of pathology or disease, or can axonal injury contribute to the spread of secondary damage, including demyelination? The former is raised from the fact that axonal damage has been reported in several virus infections, including human immunodeficiency virus, human T-lymphotropic virus 1, herpes simplex virus and coronavirus, which also cause demyelination. The latter possibility where axonal injury leads to other changes is raised from the rather unexpected similarity between spinal cord injury (SCI) and MS where axonal injury, oligodendrocyte apoptosis and demyelination are all present. In SCI, transection of axons leads to delayed oligodendrocyte apoptosis with secondary demyelination. Neurofilament immunostaining of spinal cord sections demonstrates that axonal injury with oligodendrocyte apoptosis also precedes demyelination in an animal model for MS, Theiler’s murine encephalomyelitis virus infection. This implies that axonal injury could trigger demyelination. In this instance, lesions develop from the axon (inside) to the myelin (outside) (Inside-Out model).
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影响因子：
11.2
作者：
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通讯作者：
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5.4
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14.5
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